Mixed Ligand Metal Complexes of 6-Mercaptopurine - Nicotinamide: Synthesis, Characterization, Density Functional Theory (DFT) and Biological Activity

Abstract

Spectroscopic methods were used characterized mixed ligands metal complexes of 6-mercaptopurine and nicotinamide. Density Functional Theory analysis, computational study,   biological studies were performed on the complexes. The spectroscopic analysis of the complexes supports the formation of the compounds in which the exocyclic sulphur (S-6) atom on the pyrimidine ring of the 6-mercaptopurine and its N(7) atom of the imidazole ring allows the ligand to act as bidentate while the nicotinamide coordinated as monodentate ligand only through the nitrogen atom of its pyridinic ring. Thermogravimetric analysis of the compounds is in accordance with the proposed structures. Evaluation of the thermodynamics activated parameters of the complexes shows high positive values for the ΔG and negative values for the entropy of activation which   is an indication that the decomposition of the complexes is non-spontaneous and the compounds have more ordered structure compare to the ligands. The DFT studies revealed low LUMO–HOMO energy gap (ΔE) values of  3.255eV and 1.029eV for the compounds (1) [Zn(mp)(nic)EtOH]  and (2) [Ni(mp)(nic)(Ac)].4H₂O  respectively in ethanol medium. Compound (1) [Zn(mp)(nic)EtOH] is a better antioxidant agent compare to compound (2) [Ni(mp)(nic)(Ac)].4H₂O but compound (2) shows improved  antimicrobial activity compare to compound (1). Experimental results show improved antioxidant activity for [Zn(mp)(nic)EtOH] complex which correlates with the findings from the docking experiment and the complex docked alongside allopurinol at binding pocket I with binding affinity value of  – 6.4 kcal mol⁻¹  showing its  antioxidant potential.

Keywords: 6-mercaptopurine; nicotinamide; thermodynamics activated parameters; Density Functional Theory.